An Integrated Method for Direct Interrogation of Sphingolipid Homeostasis in the Heart and Brain Tissues of Mice through Postnatal Development up to Reproductive Senescence

Sin Man Lam, Raoxu Wang, Huan Miao, Bowen Li, Guanghou Shui

Analytica Chimica Acta

Abstract

Development of rapid metabolomic methods poised for pathway discovery is expected to facilitate the identification of therapeutic candidates in the metabolomic approach to translational medicine. Using sphingolipid homeostasis as a prototype, we present herein an integrated method to facilitate a fast interrogation of altered sphingolipid (and phospholipid) metabolism associated with perturbed endolysosomal functions in mammalian systems. Constructed upon high performance liquid chromatography coupled to mass spectrometry, this method allows semi-quantitative measurements of more than 300 individual species within 20？min. The method was applied to investigate cardiac- and neural-specific developmental changes in sphingolipid regulation from the postnatal stage to reproductive senescence in mice, revealing that endogenous lysobisphosphatidic acids and specific complex glycosphingolipids are tightly co-regulated to foster concerted reductions in sphingolipid levels at distinct stages of postnatal development. Our lipidomic data suggest that such changing regulatory patterns in sphingolipid homeostasis is attributed to differential endolysosomal degradation of complex sphingolipids, which may be critical in ensuring efficient sphingolipid catabolism and organismal health at each stage of postnatal development.

论文编号:

DOI:10.1016/j.aca.2018.01.015

论文题目:

An Integrated Method for Direct Interrogation of Sphingolipid Homeostasis in the Heart and Brain Tissues of Mice through Postnatal Development up to Reproductive Senescence

英文论文题目:

An Integrated Method for Direct Interrogation of Sphingolipid Homeostasis in the Heart and Brain Tissues of Mice through Postnatal Development up to Reproductive Senescence

第一作者:

Sin Man Lam, Raoxu Wang, Huan Miao, Bowen Li, Guanghou Shui

英文第一作者:

Sin Man Lam, Raoxu Wang, Huan Miao, Bowen Li, Guanghou Shui

联系作者:

英文联系作者:

外单位作者单位:

英文外单位作者单位:

发表年度:

2018-10-31

卷:

期:

页码:

摘要:

Development of rapid metabolomic methods poised for pathway discovery is expected to facilitate the identification of therapeutic candidates in the metabolomic approach to translational medicine. Using sphingolipid homeostasis as a prototype, we present herein an integrated method to facilitate a fast interrogation of altered sphingolipid (and phospholipid) metabolism associated with perturbed endolysosomal functions in mammalian systems. Constructed upon high performance liquid chromatography coupled to mass spectrometry, this method allows semi-quantitative measurements of more than 300 individual species within 20？min. The method was applied to investigate cardiac- and neural-specific developmental changes in sphingolipid regulation from the postnatal stage to reproductive senescence in mice, revealing that endogenous lysobisphosphatidic acids and specific complex glycosphingolipids are tightly co-regulated to foster concerted reductions in sphingolipid levels at distinct stages of postnatal development. Our lipidomic data suggest that such changing regulatory patterns in sphingolipid homeostasis is attributed to differential endolysosomal degradation of complex sphingolipids, which may be critical in ensuring efficient sphingolipid catabolism and organismal health at each stage of postnatal development.

英文摘要:

Development of rapid metabolomic methods poised for pathway discovery is expected to facilitate the identification of therapeutic candidates in the metabolomic approach to translational medicine. Using sphingolipid homeostasis as a prototype, we present herein an integrated method to facilitate a fast interrogation of altered sphingolipid (and phospholipid) metabolism associated with perturbed endolysosomal functions in mammalian systems. Constructed upon high performance liquid chromatography coupled to mass spectrometry, this method allows semi-quantitative measurements of more than 300 individual species within 20？min. The method was applied to investigate cardiac- and neural-specific developmental changes in sphingolipid regulation from the postnatal stage to reproductive senescence in mice, revealing that endogenous lysobisphosphatidic acids and specific complex glycosphingolipids are tightly co-regulated to foster concerted reductions in sphingolipid levels at distinct stages of postnatal development. Our lipidomic data suggest that such changing regulatory patterns in sphingolipid homeostasis is attributed to differential endolysosomal degradation of complex sphingolipids, which may be critical in ensuring efficient sphingolipid catabolism and organismal health at each stage of postnatal development.